کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485766 | 1114366 | 2012 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Analytical Approach to Characterize the Intratumoral Pharmacokinetics and Pharmacodynamics of Gefitinib in a Glioblastoma Model
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Heterogeneity in brain tumors can result in variable drug distribution and possibly drug response; however, there are no readily accessible means to obtain regional pharmacokinetic (PK)/pharmacodynamic (PD) information in preclinical tumor models that typically rely on average drug concentration measurements. On the basis of a novel serial brain tumor sectioning protocol, sensitive and robust methods were developed to characterize the intratumoral PK [liquid chromatography with tandem mass spectrometry detection (LC/MS/MS)] and PD (phosphorylated extracellular-signal-regulated kinase, antibody-based detection) of gefitinib in small amounts of glioblastoma tumor samples obtained from mice bearing intracerebral tumors administered 150 mg/kg of gefitinib. LC/MS/MS method was accurate (±15%) and precise (coefficient of variation â¤15%). For PD analysis, two antibody-based assay systems [enzyme-linked immunosorbent assay and meso scale discovery (MSD)] were compared and the more sensitive method (MSD) was selected. Gefitinib concentrations showed up to 2.4 ± 0.7-fold intratumoral variability in PK and 1.5 ± 0.20-fold variability in PD. The methods are sufficiently accessible and could be applied to other anticancer drugs and tumor models to obtain greater resolution of intratumoral PKs and PDs. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4100-4106, 2012
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 11, November 2012, Pages 4100-4106
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 11, November 2012, Pages 4100-4106
نویسندگان
Jyoti Sharma, Hua Lv, James M. Gallo,